Skin, which is the biggest organ of the human body, is composed of epidermis, dermis and subcutaneous fat. It performs various functions such as protection, barrier, temperature controlling, excretion and respiration. With the passage of time, however, those functions rapidly decline and a variety of changes occur to the skin. Physiological changes of the skin with aging, for example, include the decrease in thickness of epidermis, dermis and subcutaneous tissue; the dryness of skin resulting from the moisture reduction according to the changes of lipid composition and content in lipid barrier; and the occurrence of age spots, freckles, pigmentation or various skin lesions. Skin aging is a complex biological process affecting various layers of the skin, but whose major effects are seen in the dermis. There are two biologically independent aging processes that occur simultaneously. The first is intrinsic aging, which affects skin as well as, most likely, the internal organs. The second is extrinsic aging or photo-aging which is the result of exposure to the elements, primarily ultraviolet irradiation. The active oxygen species and free radicals, which can be generated by excess UV rays, air pollution, or fatigue or stress in modern life, oxidize or denature the bio-materials such as proteins, nucleic acids and membrane lipids, aging of the skin. The consequences of innate aging can be observed all over the skin, including areas protected from the sun. In the areas exposed to the sun, particularly the face and the backs of the hands, photoaging damage is superimposed with tissue degeneration due to innate aging. Thus, the most noticeable changes on facial and neck skin, the primary areas that patients are concerned about, result from the combination of intrinsic and extrinsic aging processes. It has been suggested that as much as 80% of facial aging may be ascribed to exposure to the sun, although other factors (i.e. cigarette smoking) can contribute to premature wrinkling. From a biochemical standpoint, photoaging is thought though to be induced mainly by: proteases, mainly metalloproteases, which are overproduced and overrealized by keratinocytes and fibroblasts as a consequence of the interaction with ultraviolet radiation (these proteases are degradative enzymes irreversibly damaging collagen, elastin and hyaluronic acid, eliciting dermis scarring and visible wrinkles); and by oxidative stress, able to eliminate the normal skin antioxidant defenses in a very short time.
Treatments designed to prolong or promote youthful appearance include topical applications of cosmetic preparations, lotions and moisturizer, electrical stimulation, collagen injections and cosmetic surgery.
A variety of cosmetic compositions have been developed to alleviate aging of the skin and some visible results have been obtained in improving skin wrinkles. Various clinical studies have reported on the effects of cosmetic compositions containing retinoids in improving wrinkles, freckles and deposited pigments, especially of the compositions containing retinol (vitamin A) in improving wrinkles, sagging and the reduction in elasticity of skin formed by sunlight. U.S. Pat. Nos. 4,603,146 and 4,877,805 disclose methods for improving skin wrinkles by using retinol that is effective in the synthesis of collagen and the inhibition from the decomposition thereof. However, since retinol may cause skin irritation even with small doses, the use of retinol as an ingredient in cosmetics has been severely limited.
Other studies have demonstrated effectiveness of a combination of retinol and epidermal growth factor (U.S. Pat. No. 6,589,540), or other protein growth factors, alone or in combination (U.S. Pat. Nos. 5,618,544, 6,821,524, U.S. Publication Nos. 2007/0224150, 2004/0265268) or hydroxyl acid compounds (U.S. Pat. No. 7,098,189). Many of the products described in the prior art are not delivered in a sustained release manner, and further do not work by a combination of epidermal regeneration and new collagen production.
A more fundamental and comprehensive approach is needed in treating aging skin that is based on the science and biology of skin. Skin aging is a natural phenomenon that occurs over time. The primary element responsible for accelerating skin aging is overexposure to the sun's harmful rays causing photo damage. But the more important and complex causes of skin aging are biological and are caused by a slowing of the division rate of skin cells and defective cross-linking of collagen and elastin fibers in the skin. With age, the skin fails to regenerate itself as quickly as it used to, and shows common signs of aging in terms of tone and texture. Also, collagen and elastin fibers in the underlying layers of the skin, which provide the scaffolding for the surface layers, begin to weaken and deteriorate with age, causing the skin to lose elasticity and form sags, fine lines, and wrinkles.
From a biological standpoint, an effective plan for rejuvenating and repairing skin must address the rejuvenation of skin cells at both the epidermal and the dermal layers, protection of the rejuvenated cells and cellular activity, stimulation of the production of skin matrix elements, and the sustainability of the rejuvenated conditions over the long term.
It is therefore an object of the present invention to provide compositions that stimulate skin biologic activity and promote skin repair and/or regeneration.
It is a further object of the invention to provide compositions and methods of use thereof to promote skin repair and regeneration with rapid onset of skin repair and regeneration and a reduced frequency of application.